title: Membrane palmitoylated proteins regulate trafficking and processing of nectins.
abstract: Nectins are cell-cell adhesion molecules involved in the formation of various intercellular junctions and the establishment of apical-basal polarity at cell-cell adhesion sites. To have a better understanding of the roles of nectins in the formation of cell-cell junctions, we searched for new cytoplasmic binding partners for nectin. We report that nectin-1α associates with membrane palmitoylated protein 3 (MPP3), one of the human homologues of a Drosophila tumor suppressor gene, Disc large. Two major forms of MPP3 at 66 and 98 kDa were detected, in conjunction with nectin-1α, suggesting that an association between the two may occur in various cell types. Nectin-1α recruits MPP3 to cell-cell contact sites, mediated by a PDZ-binding motif at the carboxyl terminus of nectin-1α. Association with MPP3 increases cell surface expression of nectin-1α and enhances nectin-1α ectodomain shedding, indicating that MPP3 regulates trafficking and processing of nectin-1α. Further study showed that MPP3 interacts with nectin-3α, but not with nectin-2α, showing that the association of nectins with MPP3 is isoform-specific. MPP5, another MPP family member, interacts with nectins with varying affinity and facilitates surface expression of nectin-1α, nectin-2α, and nectin-3α. These data suggest that wide interactions between nectins and MPP family members may occur in various cell-cell junctions and that these associations may regulate trafficking and processing of nectins.
authors.affiliation: Department of Neuroscience, Georgetown University Medical Center, 3970 Reservoir Rd. NW, Washington, DC 20057, USA.
authors.forename: Amanda
authors.initials: A
authors.lastname: Dudak
authors.forename: Jinsook
authors.initials: J
authors.lastname: Kim
authors.forename: Bryan
authors.initials: B
authors.lastname: Cheong
authors.forename: Howard J
authors.initials: HJ
authors.lastname: Federoff
authors.forename: Seung T
authors.initials: ST
authors.lastname: Lim
mesh_terms: D000818:Animals; D015815:Cell Adhesion Molecules / Q000378:metabolism*; D002460:Cell Line; D006801:Humans; D054878:Lipoylation; D008565:Membrane Proteins / Q000737:chemistry* / Q000378:metabolism*; D000075983:Nectins; D020033:Protein Isoforms / Q000378:metabolism*; D021381:Protein Transport / Q000502:physiology*; D014018:Tissue Distribution; D020798:Two-Hybrid System Techniques
chemical_list: D015815:Cell Adhesion Molecules; D008565:Membrane Proteins; D000075983:Nectins; D020033:Protein Isoforms